- Development of dichloroacetamide pyrimidines as pyruvate dehydrogenase kinase inhibitors to reduce cancer cell growth: Synthesis and biological evaluation
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Pyruvate dehydrogenases kinases (PDKs) have recently emerged as an attractive target for anticancer treatment. Herein, we report the synthesis and biological evaluation of novel PDK1 inhibitors as anticancer agents. Of the newly synthesized compounds, N-(4,6-bis(4-(2-hydroxyacetyl)piperazin-1-yl)-2-methylpyrimidin-5-yl)-2,2-dichloroacetamide (40) is found to inhibit the growth of SF188 cancer cells with an IC50 value of 8.21 M. Isothermal titration calorimetry (ITC) experiments reveal that compound 40 directly binds to PDK1 with a Kd value of 14.7 M. Compound 40 inhibits PDK1 activity by 72.5% at a concentration of 40 , meaning it could be a useful compound to explore the pharmacology of PDK1.
- Zhang, Shao-Lin,Zhang, Wen,Xiao, Qingpin,Yang, Zheng,Hu, Xiaohui,Wei, Zhiyi,Tam, Kin Yip
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p. 78762 - 78767
(2016/09/09)
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- Synthesis of [14C]-, [13C4]-, and [ 13C4, 15N2]-5-amino-4-iodopyrimidine
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5-Amino-4-iodopyrimidine labeled with either carbon-14 or with the stable isotopes carbon-13 and nitrogen-15 was prepared starting from commercially available labeled diethylmalonate and formamide. This compound is a useful intermediate for carbon-nitrogen and carbon-carbon bond formations. Copyright
- Latli, Bachir,Jones, Paul-James,Krishnamurthy, Dhileepkumar,Senanayake, Chris H.
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- Structure-activity relationships of a series of pyrrolo[3,2-d]pyrimidine derivatives and related compounds as neuropeptide Y5 receptor antagonists
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Neuropeptide Y (NPY) has been shown to play an important role in the regulation of food intake and energy balance. Pharmacological data suggests that the Y5 receptor subtype contributes to the effects of NPY on appetite, and therefore a Y5 antagonist might be a useful therapeutic agent for the treatment of obesity. In attempts to identify potential Y5 antagonists, a series of pyrrolo[3,2-d]pyrimidine derivatives was prepared and evaluated for their ability to bind to Y5 receptors in vitro. We report here the synthesis and initial structure-activity relationship investigations for this class of compounds. The target compounds were prepared by a variety of synthetic routes designed to modify both the substitution and the heterocyclic core of the pyrrolo[3,2-d]pyrimidine lead 1. In addition to identifying several potent Y5 antagonists for evaluation as potential antiobesity agents, a pharmacophore model for the human Y5 receptor is presented.
- Norman,Chen,Chen,Fotsch,Hale,Han,Hurt,Jenkins,Kincaid,Liu,Lu,Moreno,Santora,Sonnenberg,Karbon
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p. 4288 - 4312
(2007/10/03)
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- Dinucleotide-analogous tetrapeptides. Specific triplex formation with complementary polynucleotides
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Several tetrapeptides (1-4) having two adenyl moieties at the side chains interacted complementary base-specifically with poly (dT) or poly (U). The hypochromic effects and CD spectra of the complexes suggested the formation of triplexes, which are more stable than those between natural ApA and the polynucleotides.
- Yamazaki, Takahisa,Komatsu, Kazunori,Umemiya, Hiroki,Hashimoto, Yuichi,Shudo, Koichi,Kagechika, Hiroyuki
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p. 8363 - 8366
(2007/10/03)
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